Background

Age-related macular degeneration (AMD) is a major cause of severe visual loss in elderly people. The treatments for dry AMD (dAMD) are severely limited so far. In this work, we aim to develop an eye drop to protect retinal functions against oxidative stress and apoptosis for improving dAMD management.

Methods

Astragaloside-IV (ASIV) was prepared into phospholipid complex and loaded into three sizes (20, 50 and 90 nm) of ASIV lipid nanocapsules (ASIV-LNCs). The penetration and distribution of LNCs were investigated. DAMD mice model was induced by NaIO₃, and therapeutic effect was evaluated by electroretinography (ERG), histological examination, apoptosis and ROS detection.

Results

The ocular penetration and pharmacokinetic studies corroborated the feasibility of the LNCs to reach the fundus, and ultra-small-size LNCs (ASIV-LNCs-20) had the best delivery effect. ASIV-LNCs-20 was able to decrease ROS production and reduce the apoptosis rate from 5.12% to 0.533%. ERG and H&E staining results confirmed ASIV-LNCs-20 had a good protective effect on the morphology and function of the retina.

Conclusions

These results suggest that ASIV-LNCs can be a promising therapy approach for dAMD, and this research also offers new possibilities for further applications of LNCs as a drug delivery system for other eye diseases.

Abbreviations

AMD: Age-related macular degeneration;AREDS Age-related eye disease study; ASIV: Astragaloside-IV;AUC: Area under the concentration-time curve; dAMD: Dry age-related macular degeneration; DHE: Dihydroethidium; DL: Drug Loading; DLS: Dynamic light scattering; DSC: Differential scanning calorimetry; EE: Entrapment efficiency; ELSD: Evaporative light scattering detector; ERG: Electroretinographic; H&E: Hematoxylin and Eosin; I.S.: Internal standard; LB: Langmuir-Blodgett; LNCs: Lipid nanocapsules; MCT: Medium-chain triacylglycerol; ONL: Outer nuclear layer; OPL: Outer plexiform layer; PDI: Polydispersity index; PR: Photoreceptor;ROS: Reactive oxygen species; RPE: Retinal pigment epithelium; TEM: Transmission electron microscope; wAMD: Wet age-related macular degeneration

中文翻译：

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超小型黄芪甲苷-IV脂质纳米胶囊滴眼液，可有效治疗与干龄相关的黄斑变性。

背景

与年龄有关的黄斑变性（AMD）是老年人严重视力丧失的主要原因。迄今为止，干性AMD（dAMD）的治疗受到严重限制。在这项工作中，我们旨在开发一种滴眼剂，以保护视网膜功能免受氧化应激和细胞凋亡的影响，从而改善dAMD的管理。

方法

将黄芪甲苷IV（ASIV）制成磷脂复合物，并装入三种尺寸（20、50和90 nm）的ASIV脂质纳米胶囊（ASIV-LNCs）中。研究了LNC的渗透和分布。NaIO ₃诱导DAMD小鼠模型的建立，并通过视网膜电图（ERG），组织学检查，细胞凋亡和ROS检测来评价疗效。

结果

眼部渗透和药代动力学研究证实了LNC到达眼底的可行性，并且超小型LNC（ASIV-LNCs-20）的递送效果最佳。ASIV-LNCs-20能够降低ROS的产生并将细胞凋亡率从5.12％降低至0.533％。ERG和H＆E染色结果证实ASIV-LNCs-20对视网膜的形态和功能具有良好的保护作用。

结论

这些结果表明，ASIV-LNCs可能成为dAMD的有前途的治疗方法，这项研究也为将LNCs用作其他眼部疾病的药物输送系统提供了新的可能性。

缩略语

AMD：与年龄有关的黄斑变性； AREDS与年龄有关的眼病研究；ASIV：黄芪甲苷-IV； AUC：浓度-时间曲线下的面积；dAMD：与干龄相关的黄斑变性；DHE：二氢乙啶；DL：药物装载；DLS：动态光散射；DSC：差示扫描量热法；EE：诱捕效率；ELSD：蒸发光散射检测器；ERG：视网膜电图；H＆E：苏木精和曙红；IS：内标；LB：Langmuir-Blodgett；LNCs：脂质纳米胶囊；MCT：中链甘油三酯；ONL：外核层；OPL：外丛状层；PDI：多分散指数；PR：感光体； ROS：活性氧；RPE：视网膜色素上皮；TEM：透射电子显微镜；wAMD：与年龄有关的湿性黄斑变性